Longitudinal Evaluation of Effects of Intra-Articular Mesenchymal Stromal Cell Administration for the Treatment of Osteoarthritis in an Ovine Model

Abstract

In this study, the therapeutic effect of intra-articularly injected autologous mesenchymal stromal cells (MSCs) was evaluated in an ovine osteoarthritis (OA) model using consecutive magnetic resonance imaging (MRI), radiography, and macroscopic and histologic postmortem examination. In 12 sheep, OA was induced by bilateral, lateral meniscectomy. After 6 weeks, 20 × 10 6 bone marrow-derived MSCs (50% MSCs were superparamagnetic iron oxide particle labeled) were injected intra-articularly into one knee joint. The contralateral knee served as negative control. MR images were acquired before OA induction, immediately before and after MSC injection, and 1, 4, 8, and 12 weeks thereafter using a 0.5T unit and a T2* gradient echo sequence. Radiographs were obtained before OA induction, at MSC injection, and 12 weeks thereafter. The MRI scoring system included articular cartilage, bone, joint capsule, and synovial fluid evaluation. The radiographic scoring system included the joint space and bone. Postmortem evaluation entailed macroscopic and histologic assessment. Longitudinal MRI revealed a significant deceleration of OA progression in MSC-treated joints. However, at the conclusion of the study, there was no significant difference in the degree of OA detected by MRI, radiography, and postmortem evaluation between the treatment and control group. The degree of OA on MRI varied among the 12 animals at the time of injection, but there was no difference between the left and right limb. In conclusion, intra-articular MSCs decreased OA progression. However, no significant treatment effects were seen at the conclusion of the study at 12 weeks. This somewhat contradicts previously published results. Nevertheless, the choice of OA model, outcome measures, or lack of additional medication might explain the differences. Our results indicate that OA might benefit from intra-articular MSC injection, but further studies are needed to refine patient selection and injection parameters for a more substantially improved outcome.